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Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin

Phase 2
18 Years
Open (Enrolling)
Cutaneous Leiomyomas, Hereditary Leiomyomatosis and Renal Cell Cancer

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Trial Information

Randomized Pilot Study for the Treatment of Cutaneous Leiomyomas With Botulinum Toxin


- Cutaneous leiomyomas are smooth muscle tumors that may arise sporadically or in
association with an inherited cancer-related genodermatosis.

- Leiomyomas may be severely painful, and current management is generally unsatisfactory.

- Studies demonstrate increased nerve density within and around leiomyomas as well as
increased acetylcholinesterase staining of associated nerves.

- Botulinum toxin-A has been used in the treatment of pain syndromes.

- Based on the known mechanisms of action of botulinum toxin-A, treatment with botulinum
toxin-A (BOTOX; Allergan, Inc.), may ameliorate the severe paroxysmal pain of
symptomatic cutaneous leiomyomas.


- Primary: To assess change in worst lesional pain in the past week based on Brief Pain
Inventory (BPI) from Week 0 to Week 4 in treated patients versus controls.

- Primary: To assess improvement in pain based on Visual Analog Scale (VAS) after
application of ice at Week 4 compared to baseline in treated patients versus controls.

- Secondary: To assess change in magnitude and in frequency of painful episodes based on
a weekly patient diary in treated patients versus controls.

- Secondary: To assess persistence of pain control at Weeks 12 based on the BPI and VAS.

- Secondary: To assess the frequency of rescue pain medication use in treated patients
versus controls during the 24 week study period.

- Secondary: To determine the impact of leiomyoma treatment on quality of life.

- Secondary: To assess change in patient's condition based on the Patient Global
Impression of Change.

- Secondary: To evaluate the immunohistochemical staining of nerve fibers and muscle in
cutaneous leiomyomas in control and treated lesions following the conclusion of the


- Subjects greater than or equal to18 years with at least 1 symptomatic cutaneous

- Pain symptoms must occur at least once a week and be characterized as greater than or
equal to 5 out of 10.


- A 12-week double-blind placebo controlled pilot study of 18 subjects with symptomatic
leiomyomas will include initial assessment with BPI, photography, and skin biopsies,
followed by treatment of subjects who initially received placebo.

- Cutaneous leiomyomas will undergo intralesional injection with botulinum toxin-A.

- Subjects will return at Weeks 4 and 12 for repeat assessment using pain and quality of
life questionnaires and photography. Skin biopsies will be performed at week 12.

Inclusion Criteria


1. Subjects must be age greater than or equal to18 years.

2. Subjects must have a prior biopsy-proven diagnosis of cutaneous leiomyoma.

3. Subjects must have at least 1 symptomatic leiomyomas or regions less than or
equal to 60 cm(2) of leiomyomas with pain characterized as greater than 4 based
on a 10-point scale, indicating pain of at least moderate severity.

4. Pain episodes must occur at least once a week.

5. Subjects must have the ability to participate fully and comply with the
procedures of the protocol in the opinion of the investigator.

6. Written informed consent has been obtained including consenting to have tissue
samples stored, however subjects are allowed to refuse sample storage.

7. Negative urine or serum pregnancy test in females of childbearing potential.

8. Subjects who are clinically stable such that they can be expected to complete
the 24-week study.


1. Subjects with allergies to BTX-A.

2. Females with a positive pregnancy test, or who are breast-feeding, planning a
pregnancy during the study, who think that they may be pregnant at the start of the
study or females of childbearing potential who are unable or unwilling to use a
reliable form of contraception during the study.

3. Subjects with neuromuscular junction disorders (ie. myasthenia gravis or
Lambert-Eaton syndrome) or peripheral motor neuropathic diseases (ie. amyotrophic
lateral sclerosis or motor neuropathy).

4. Subjects with infection at the intended sites of injection.

5. Subjects who have had prior Botulinum toxin product within the past 6 months.

6. Subjects with pain resulting from other disease(s), specifically:

- pain that requires intermittent or ongoing treatment with narcotics

- severe, debilitating, or acute pain originating from sources other than

7. Subjects taking pain medications, neuroactive agents, or other therapy directed
toward treatment of cutaneous leiomyomas concurrently or within 5 days or 5
half-lives (whichever is longer) of BTX-A treatment, other than specified rescue pain
medications). Patients currently on therapy directed toward OTHER mild to moderate
chronic pain will be evaluated on a case-by-case basis for inclusion. Patients with
well-controlled mild to moderate chronic pain such as that associated with
osteoarthritis, who do not require narcotic therapy, will NOT be excluded. Aspirin
for pain relief or for other indications is also acceptable.

8. Subjects with late-stage cancers or unstable disease (such as hemodynamic
instability, i.e., systolic or diastolic blood pressure fall of 20 mm Hg or greater
from the stable patient's baseline measurement).

9. A condition or situation that, in the investigator's opinion, may put the subject at
significant risk or interfere significantly with the subject's participation in the

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

Worst lesional pain as measured by the Brief Pain Inventory (BPI) at baseline and at 4 and 12.

Safety Issue:


Principal Investigator

Edward W Cowen, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

January 2009

Completion Date:

December 2013

Related Keywords:

  • Cutaneous Leiomyomas
  • Hereditary Leiomyomatosis and Renal Cell Cancer
  • Cutaneous Leiomyomas
  • Skin Pain
  • Botox Therapy
  • Hereditary Leiomyomatosis
  • Renal Cell Cancer
  • Cutaneous Leiomyoma
  • Carcinoma, Renal Cell
  • Leiomyoma
  • Myofibroma
  • Leiomyomatosis
  • Kidney Neoplasms
  • Neoplastic Syndromes, Hereditary



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892